The inflammatory response to sciatic nerve injury in a familial amyloidotic polyneuropathy mouse model

Exp Neurol. 2014 Jul;257:76-87. doi: 10.1016/j.expneurol.2014.04.030. Epub 2014 May 5.


Inflammation is a hallmark of several neurodegenerative disorders including familial amyloidotic polyneuropathy (FAP). FAP is associated with extracellular deposition of mutant transthyretin (TTR), leading to degeneration of cells and tissues, particularly in the peripheral nervous system (PNS). With this work, our goal was to characterize the expression/deposition of TTR and the associated inflammatory immune response, induced by nerve injury, in WT mice and in a mouse model carrying the most common TTR mutation in FAP (V30M). Our results indicate that upon nerve injury TTR is significantly produced by Schwann cells and is dynamically regulated over time in V30M mice, accompanying a peak of inflammation. Strikingly, V30M TTR deposition in nerve tissue occurred, suggesting that inflammation contributes to TTR polymerization. In response to nerve injury, V30M mice display a downregulated innate immune response when compared to WT mice. More specifically, we saw decreased expression of cytokines and chemokines important for the recruitment of immune cells like macrophages and neutrophils, known to be important for the tissue regenerative process which was found impaired in V30M mice. In conclusion, with this work we were able to characterize the biology of TTR both in WT and V30M animals, upon nerve injury, and found that V30M TTR impairs the inflammatory response necessary for nerve regeneration. Taken together, our findings suggest that inflammation is an important target to be considered in therapeutic strategies for FAP.

Keywords: Cytokines; Inflammation; Nerve injury; Neuroinflammation; Regeneration; Schwann cells; Transthyretin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / physiopathology*
  • Animals
  • Disease Models, Animal
  • Female
  • Functional Laterality / genetics
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism*
  • Locomotion / genetics
  • Male
  • Methionine / genetics
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Pain Measurement
  • Prealbumin / genetics
  • Prealbumin / metabolism
  • Schwann Cells / metabolism
  • Sciatic Neuropathy / blood
  • Sciatic Neuropathy / complications*
  • Sciatic Neuropathy / pathology*
  • Time Factors
  • Valine / genetics


  • Prealbumin
  • Methionine
  • Valine